The proposed research is a study of the effects of low doses (sublethal) of ultraviolet (UV) and ionizing radiation on cultured human diploid fibroblasts (HDF). Emphasis is on 1. defining the effects of these radiations on arrested non-mitotic populations of various HDF strains and 2. inducing with these radiations HDF transformants in culture. A fraction of cells from UV-irradiated arrested populatons is lost upon subsequent incubation. The extent of cell loss is dose dependent and cell strain specific. A xeroderma pigmentosum (XP) strain is more sensitve to UV than are normal HDF. The sensitive target appears to be DNA. The lethal event appears to be one on RNA transcription that leads to an inhibition of required protein synthesis. Experiments are proposed to study this effect in XP strains from other complementation groups and the parental presumed heterozygotes. Mechanisms of DNA repair will be studied in these non-dividing cells. The objective is to define the significance of DNA repair in this assay. Other experiments to induce and detect HDF transformants in culture are proposed. Emphasis is placed on using HDF strains isolated from individuals with a predisposition to cancer, using fresh primary isolates (1st passage), using X-rays and UV with chemicals defined as co-carcinogens (phorbol esters, diethylstilbestrol, anthralin), and using various culture procedures that may permit expression of a transformation event.